Effect of hepatic disease on the pharmacokinetics and plasma protein binding of eprosartan.
OBJECTIVE
To evaluate the pharmacokinetics and plasma protein binding of eprosartan in hepatic disease.


METHODS
Single-dose, parallel-group study.


METHODS
Oklahoma Foundation for Digestive Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.


METHODS
Eight healthy subjects with normal hepatic function and eight patients with hepatic disease.


METHODS
All subjects received a single oral dose of eprosartan 100 mg.


RESULTS
Eprosartan plasma concentrations were quantified by high-performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Using analysis of variance, point estimates (PE) and 90% CIs were calculated. Total and unbound maximum concentrations and degree of plasma protein binding were similar for both groups. Total area under the plasma concentration-time curve (AUC0-t) was approximately 40% higher for the group with hepatic disease (PE 1.42, 90% CI 0.94-2.14). Similarly, unbound AUC0-t was approximately 50% higher (PE 1.53, 90% CI 0.98-2.39).


CONCLUSIONS
Eprosartan was safe and well tolerated by both groups. Based on the increase in AUC in patients with hepatic disease compared with those with normal hepatic function, the dosage of eprosartan in patients with hepatic disease should be individualized based on tolerability and response.
Tenero
D
D
Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Martin
D
D
Chapelsky
M
M
Ilson
B
B
Boike
S
S
Patterson
S
S
Keogh
J
J
Rodriguez
S
S
Jorkasky
D
D
D000179:Acrylates / Q000493:pharmacokinetics*; D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan